It was shown that small fractions of auto-Abs can possess different catalytic activities

It was shown that small fractions of auto-Abs can possess different catalytic activities

cytometry, the number of tumor cells 7 sIL-2R in Debio1347 site B-cell Lymphomas Disease DLBCL site No. of cases 54 Age, median 69 67 72 55 54 sIL-2R, median 1313.5 1404 1013 1742 472.5 No. of CD68-macrophages median 45.7 45 46.6 23.8 12.8 No. of CD163macrophages median 25 27.8 20.6 23.8 1.6 nodal extranodal FL RLH intrafollicular 31 23 19 11 Abbreviations: sIL-2R; Soluble Interleukin-2 Receptor, DLBCL; Diffuse large B-cell lymphoma, FL; Follicular lymphoma, RLH; reactive lymph node hyperplasia. doi:10.1371/journal.pone.0078730.t002 or normal T lymphocytes expressing CD25 did not reflect sIL-2R levels. This indicates the existence of other factors responsible for production of sIL-2R, and we considered MMP-9 to be the main factor responsible for production of sIL-2R through cleavage of the IL-2R a chain expressed on lymphoma cells and bystander Tcells. To characterize the functional effects of MMP-9 on IL-2R cleavage, MT4 with CD25 on their surfaces and not showing endogenous MMP-9 were analyzed. Experiments in such cells cultured with rMMP-9 and MMP-9 inhibitor confirmed MMP-9 cleavage of IL-2Ra chains on malignant lymphoma cells. Expression of MMP-9 in B-cells containing lymphoma cells in DLBCL and FL was detected on gelatin zymography, but not on IHC. On the other hand, IHC study revealed that the macrophages in the tumor microenvironment were slightly positive for MMP-9 in samples of DLBCL and FL samples. Therefore, the main source of MMP-9 could be macrophages and B-cells containing lymphoma cells are also the producer of MMP-9 in tumors. Contribution of CD68-positive macrophages to elevation of sIL-2R Several reports have shown that TAMs are related to poor prognosis and tumor progression in malignant tumors, including lymphoma, and we also believed that TAMs are responsible for production of sIL-2R as they were positive for MMP-9 on IHC analysis. Interestingly, we 12642398 found that there were positive correlations between the number of CD68-positive macrophages and the levels of sIL-2R in FL and extranodal DLBCL. On the other hand, the numbers of CD163-positive macrophages are not related to the levels of sIL-2R. Previous data of gene expression profiling of macrophages and monocytes was adapted in an effort to determine whether the expression levels of CD68 are correlated with those of MMP-9. The results revealed positive correlations between the expression levels of CD68 and those of MMP-9, thus the number of CD68-positive macrophages may be correlated with sIL-2R levels. In addition, the expression levels of other enzymes were also correlated with those of CD68 in macrophages/monocytes . Among them, MMP-2, which is a gelatinase containing gelatin binding repeat as well as MMP-9, is thought to have the effect of cleavage of a chain of IL-2R, although the expressions of MMP-2 were lower than those of MMP-9. Since these enzymes may affect sIL-2R levels, no apparent correlations between sIL-2R levels and MMP-9 levels may be observed in patients with DLBCL and FL. TAMs in DLBCL DLBCL is a heterogeneous group of B-cell lymphoma, and is classified into activated B-cell -type DLBCL, germinal 8 sIL-2R in B-Cell Lymphomas center B-cell -type DLBCL and primary mediastinal B-cell type DLBCL based on gene expression profile. According to the Hans 10408253 algorithm of DLBCL, our study includes 9 cases of GCB-type DLBCL and 2 cases of non-GCB type DLBCL. However, apparent correlations were not observed among the types of DLBCL, and the number of CD68-positive and CD163po

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